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Results of Induction Chemotherapy in Children Older Than 1 Year With a Stage 4 Neuroblastoma Treated With the NB 97 French Society of Pediatric Oncology (SFOP) Protocol

From the Pediatrics Department, Statistics Department, Institut Gustave Roussy, Villejuif Cedex; Pediatrics Department, Institut Curie, Paris; Nuclear Medicine Department, Institut Claudius Regaud; Onco-hematology Unit, CHU Purpan, Toulouse; Onco-hematology Department, CHU Pellegrin, Bordeaux; Pediatrics Department, Centre Léon Bérard, Lyon; Pediatric Oncology Unit, CHU La Timone, Marseille; Pediatric Oncology Unit, CHU, Grenoble; Pediatric Oncology Unit, Hopital St Charles, Montpellier; Pediatric Oncology Unit, CHR, Hopital d'Enfants Brabois, Vandoeuvre, France

Address reprint requests to Dominique Valteau-Couanet, MD, PhD, Département de Pédiatrie, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France; e-mail: valteau{at}igr.fr

PURPOSE: To test the metastatic response rate in stage 4 neuroblastoma, using dose-intensive induction chemotherapy in a multi-institutional setting.

PATIENTS AND METHODS: From 1998 to 1999, 47 consecutive children were treated according to N7 protocol. Children received cyclophosphamide 140 mg/kg, doxorubicin 75 mg/m², and vincristine 0.066 mg/kg (CAV) in cycles 1, 2, 4, and 6, and cisplatinum 200 mg/m² and etoposide 600 mg/m² (P/VP) in cycles 3, 5, and 7. The International Neuroblastoma Staging system was used with an emphasis on skeletal evaluation by 123-iodine-metaiodobenzylguanidine (MIBG) scintigraphy. A phase II study evaluating the metastasis complete response rate after induction chemotherapy was conducted in patients who had positive metastatic sites on MIBG scans at diagnosis.

RESULTS: Forty-six patients were assessable for toxicity. Hematologic toxicity was the main toxicity observed. Neutropenia was more frequent after CAV than after P/VP (P < .001). A higher rate of thrombocytopenia was observed after P/VP (P = .03). Forty patients with positive MIBG were assessable for metastatic response, and complete regression of metastases was achieved in 17 patients (ie, 43%; 95% CI, 27% to 59%). Of all 47 patients, 21 achieved complete metastatic response.

CONCLUSION: The N7 induction chemotherapy protocol was feasible in a multicentric setting. The observed metastasis complete response rate was similar to that obtained in our previous studies and significantly lower than that published in a previous series using the same regimen. In our hands, escalating doses of cyclophosphamide and prolonging conventional chemotherapy with the same drugs failed to improve the metastasis complete response rate.

Supported by a grant from Amgen, Neuilly sur Seine Cedex, France.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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